We recently corrected sickle cell disease in our knockin mouse model by reprogramming skin fibroblasts into iPS (induced Pluripotent Stem) cells, replacing the defective sickle beta-globin gene with a normal beta-globin gene, differentiating the corrected iPS cells into hematopoietic progenitors and transplanting these cells into irradiated sickle mouse recipients. The goal of the present proposal is to translate these results to human cells. The specific aims are (1) to produce human iPS cells from skin biopsy samples of patients with sickle cell disease (2) to correct the sickle mutation in iPS cells derived from patients and (3) to differentiate corrected iPS cells into transplantable hematopoietic stem cells that produce normal erythroid cells.